Isorhamnetin represses adipogenesis in 3T3-L1 cells.
Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.
Lee
Jongsung
J
Biospectrum Life Science Institute, Gunpo City, Gyunggi Do, Republic of Korea.
Jung
Eunsun
E
Lee
Jienny
J
Kim
Saebom
S
Huh
Sungran
S
Kim
Youngsoo
Y
Kim
Yongwoo
Y
Byun
Sang Yo
SY
Kim
Yeong-Shik
YS
Park
Deokhoon
D
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D044948:Flavonols / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D051767:Early Growth Response Protein 2; D044948:Flavonols; D047495:PPAR gamma; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; C047368:3-methylquercetin; D011794:Quercetin; D005993:Glycerolphosphate Dehydrogenase